HIV
Conditions
Interventions
Trade Name: Dovato
Product Name: Dovato
Pharmaceutical Form: Tablet
INN or Proposed INN: Dolutegravir
Other descriptive name: DOLUTEGRAVIR SODIUM
Concentration unit: mg milligram(s)
Concentration type
Sponsors
Seimc-Gesida Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. Adults (? 18 years old) with HIV-1 infection able to understand and give informed written consent. b. Stable ART in the 12 weeks prior to screening visit. - Only switch for tolerability/convenience/access reasons to generic drugs or switch from ritonavir to cobicistat or TDF to TAF would be allowed in the 12-week window and as long as the components of the regimen are unchanged. c. Viral load 200 cel/µL at screening. e. History of 3TC resistance: either confirmed historical 3TC resistance (historical RNA Sanger or RNA NGS>20% threshold genotype with M184V/I mutation) OR suspected historical 3TC resistance. - Suspicion of past 3TC resistance is defined as any of the following: i. Previous treatment with only 2 NRTIs (1 of them being emtricitabine or 3TC [XTC]). ii. Two consecutive VL > 200 cp/mL while on treatment including XTC. iii. One VL > 200 cp/mL while on treatment including XTC PLUS change of ART as consequence of that elevated VL. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 117 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 117
Exclusion criteria
Exclusion criteria: a. Participants with M184V/I or K65R in screening visit proviral DNA Sanger genotype. b. Prior virologic failure (VF) under integrase inhibitor (INSTI)- based regimen. defined as two consecutive VL > 200 copies/mL while receiving INSTI regardless of genotypic test results c. INSTI resistance mutations in historical RNA genotype. d. Positive Surface Hepatitis B Ag (HBAgS) OR negative HBAgS and negative hepatitis B surface antibody (anti-HBs) with positive anti-core antibody (anti- HBc) and positive HBV DNA. e. Pregnant, breastfeeding women, women with a positive pregnancy test at the time of screening, sexually active fertile women wishing to conceive or unwilling to commit to contraceptive methods (see Appendix 1 for the accepted list of the highly effective methods for avoiding pregnancy), for the duration of the study and until 4 weeks after the last dose of study medication. All women are considered fertile unless they have undergone a sterilizing surgery or are over the age of 50 with spontaneous amenorrhea for over 12 months prior to study entry. f. Patients with active opportunistic infections or cancer requiring intravenous treatment and/or chemotherapy at screening. g. Any comorbidities or treatment with experimental drugs that according to the investigator could bias study results or entail additional risks for the participant. h. Participants receiving other medications that according to study drug label are contraindicated. i. Severe hepatic impairment (Class C) as determined by Child-Pugh classification. j. Alanine aminotransferase (ALT) over 5 times the upper limit of normal (ULN) or ALT over 3xULN and bilirubin over 1.5xULN. k. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones); l. Creatinine clearance of <30 mL/min/1.73m2 via CKD-EPI method. m. Any verified Grade 4 laboratory abnormality that to the investigators criteria would affect the safety of the participant if included in the study. n. History or presence of allergy to dolutegravir or lamivudine.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of a switch to DTG/3TC for maintenance of virologic suppression at 48 weeks in persons with past confirmed or suspected 3TC resistance, when proviral DNA population sequencing does not detect 3TC resistance-associated mutations at baseline.;Secondary Objective: - To evaluate other estimations of virological control at weeks 48 and 96. - To assess viral resistance in persons experiencing VF - To evaluate factors associated with VF. -To assess the impact of baseline archived minority 3TC resistance-associated mutations in viral control (in cases of VF and transient viral rebounds [VL=50copies/mL preceded and followed by VL<50 copies / Ml). - To evaluate the dynamics of archived minority 3TC resistance-associated mutations after switching to DTG/3TC at 96 weeks. - To evaluate the immune effects of switch to DTG/3TC - To evaluate the safety and tolerability of DTG/3TC in this study;Primary end point(s): Proportion of virologic failure (VF) defined as HIV-1 RNA viral load (VL) = 50 copies per mL at 48 weeks (in the intention-to-treatexposed population (ITT-e) using the US Food and Drug Administration (FDA) snapshot algorithm).;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of VF (=50 copies/mL) at week 96, ITT-e, FDA snapshot. - Proportion of VF (=50 copies/mL) atweek 48 and 96, per protocol population (PP), FDA snapshot. - Proportion of VF (=200 copies/mL) at week 48 and 96, ITT-e and PP population, FDA snapshot. - Proportion of Confirmed Virologic Withdrawal ([CVW]: A VL= 50 copies/mL followed by a VL= 200 copies/mL in retest) at weeks 48 and 96, ITT-e and PP population, FDA snapshot. - Proportion of Precautionary Virologic Withdrawal ([PVW]: three consecutive VL between 50- 200 copies/mL) at weeks 48 and 96, ITT-e and PP population, FDA snapshot. - Proportion of participants with VL<50 copies/mL week 48 and 96, ITT-e and per protocol population, FDA snapshot. - Incidence of VF with drug resistance aations.ssociated mut - Describe number and type of resistanceassociated mutations in VF - Analysis of factors associated to VF (i.e time to VF). - Proportion of VF in pre-specified subgroups: - Confirmed historical M184V/I vs No resistance mutations - INSTI exposure vs No prior INSTI exposure - Time virologically suppressed - Time on 3TC/FTC - Proportion of participants with VF with baseline 3TC or INSTI resistanceassociated mutations detected at baseline by NGS with 1, 5, and 20% threshold. - Proportion of participants with transient viral rebounds with baseline 3TC or INSTI resistance- associated mutations detected at baseline by NGS with 1, 5, and 20% threshold. - Type and frequency of resistance mutations (RT and integrase) in proviral DNA measured by NGS at baseline and week 96. - Change from Baseline in CD4+ cell count and in CD4+/CD8+ cell counts ratio at weeks 48 and 96 -Incidence and severity of AEs and laboratory abnormalities through week 48 and 96. - Proportion of subjects who discontinue treatment due to AEs through weeks 48 and 96.;Timepoint(s) of evaluation of this end point: Weeks 48 and 96 | — |
Countries
Spain
Contacts
Public ContactMaria Yllescas
Seimc-Gesida Foundation
Outcome results
None listed